Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons and eventually results in death. A number of genes have been associated with ALS, including superoxide dismutase 1 (SOD1), fused in sarcoma/translocated in liposarcoma (FUS/TLS), and to the loss of normal TAR DNA-binding protein 43 (TDP-43), survival of motor neuron (SMN) and others. There is currently no cure for ALS.
Survival of motor neuron (SMN) is a protein involved in transcriptional splicing through its involvement in assembly of small nuclear ribonucleoproteins (snRNPs). snRNPs are protein-RNA complexes that bind with pre-mRNA to form a spliceosome, which then splices the pre-mRNA, most often resulting in removal of introns. Three genes encode SMN or a variant of SMN, including SMN1 (survival of motor neuron 1, telomeric), SMN2 (survival of motor neuron 2, centromeric), and SMNP (survival of motor neuron 1, telomeric pseudogene). SMN1 and SMN2 are a result of a gene duplication at 5q13 in humans. A lack of SMN activity results in widespread splicing defects, especially in spinal motor neurons, and degeneration of the spinal cord lower motor neurons.